This invention relates generally to medical methods and devices and, more particularly, relates to methods and apparatus for analysis of diastolic function.
Cardiologists examining heart function face a challenging analytical task. In theory, pressure and volume data from the heart chambers should provide important information regarding heart muscle function. However, analysis of pressure-volume data from the heart is complex because pressures and volumes both depend on simultaneously variable factors such as preload, afterload, and contractility.
Maximum elastance (Emax), or the slope of the end-systolic pressure volume relation (ESPVR), serves as a physiologically useful, load independent index of systolic function. (H. Suga et al., “Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio”, Circ Res 32: 314 (1973); K. Sugawa et al., “End-systolic pressure-volume ratio: a new index of ventricular contractility”, Am J Cardiol 40: 748 (1977)) Modeling the ventricle as a time varying elastance has permitted the derivation and validation of Emax, which has thereby provided a characterization of left ventricle (LV) chamber contractility. Such an approach is based on the finding that that the instantaneous pressure to volume ratio in the heart, where the volume is measured relative to a “lax” volume Vo, defines a time-varying elastance. The time-varying elastance attains the same maximum value at a fixed contractile state regardless of changes in load. Thus Emax is known as a valid load-independent index of systolic function. Additional conceptual validation of Emax as a load independent index of systolic function has been achieved using a kinematic, forced harmonic oscillator-based argument showing that the slope of the maximum force-displacement relationship (ESPVR analog) depends only on the intrinsic parameters of the oscillator rather than the initial conditions (load). (B. Oommen et al., “Modeling Time Varying Elastance: The Meaning of “Load-Independence”, Cardiovascular Engineering 3(4): 123-130 (2003)).
Emax has been found to be well approximated by the ESPVR. Furthermore, enhanced contractile states, achieved through epinephrine stimulation, generate higher maximum elastance values. Thus, Emax is an accepted, load-independent measure of contractility. Although it is known that the global end-systolic P-V (elastance) relation is curvilinear, a linear approximation is justified because the amount of nonlinearity in the physiologic range is modest.
While Emax is a chamber property which is uncoupled from the effects of load on systolic function, no equivalent load-independent property or measure has been predicted to exist, nor has one been experimentally (empirically) discovered, for diastole. Thus, in contrast to the ‘load-independent index of systolic function’ problem, the ‘load-independent index of diastolic function’ problem remains to be solved. For example, echocardiographic global diastolic function assessment utilizes a broad array of transmitral flow or tissue motion-based indices that are known to be load-dependent. Conventional approaches to diastolic function (DF) index determination have been primarily correlative, and have not yielded a load independent index of DF (LIIDF).
Echocardiography is a preferred and accepted noninvasive method for DF assessment. Doppler echocardiography derived indices have been used to characterize DF in numerous cardiac disorders including heart failure, myocardial infarction, reversible myocardial ischemia, hypertrophic cardiomyopathy, and hypertension (S. J. Kovács et al., “Can Transmitral Doppler E-waves Differentiate Hypertensive Hearts From Normal?” Hypertension 30: 788-795 (1997)). Pulsed wave Doppler echocardiography is used for transmitral flow assessment. In current practice, most DF indices are derived by visual inspection of transmitral E- and A-wave shape. There are dozens of shape-derived indices, the most common ones include: the peak velocity of the E-wave (Epeak), the duration of the E-wave (Edur), the acceleration and deceleration times of the E-wave (AT and DT) and the area under the E-wave (velocity-time integral, VTI). Additional indices include the peak velocity of the A wave (Apeak) and the ratio of the E and A peak velocities (E/A). However, most of the clinically relevant Doppler derived DF indices have proven to be load dependent. (S. J. Kovács et al., “Modeling of Diastole”, Cardiology Clinics of North America 18(3): 459-490 (2000); S. J. Kovács et al., “Modeling cardiac fluid dynamics and diastolic function”, Philosophical Transactions of the Royal Society (A)359: 1299-1314 (2001)). To date, E/E′, (the ratio of Epeak to the mitral annular peak velocity E′), measured by Doppler tissue imaging, is the sole DF index for which its relation to LVEDP, i.e. its load dependence, has been characterized based on first principles (J. B. Lisauskas et al., “The Relation of the Peak Doppler E-wave to Peak Mitral Annulus Velocity Ratio to Diastolic Function”, Ultrasound in Medicine and Biology 27(4): 499-507 (2001)).
In addition, non-invasive indexes derived from Doppler echocardiography have been used to estimate invasively derived left ventricular pressures. Left ventricular pressures, such as the minimum diastolic (filling phase) pressure (LVPmin), the end-diastolic pressure (LVEDP), the diastasis or pre-A wave pressure, as well as the average filling pressure, are invasive measures that are employed in clinical practice to aid in patient management and diagnosis. Swan-Ganz catheter pulmonary capillary wedge pressure (PCWP) is also an important invasive measure that is routinely employed clinically as a surrogate for the atrial pressure and used for diagnosis and monitoring. Gold standard determination of these mentioned pressures requires invasive catheterization, and numerous studies, over the last two decades, have attempted to estimate invasive pressures with the aid of Doppler echocardiography. See, e.g., Kuecherer HF et al. “Determination of left ventricular filling parameters by pulsed Doppler echocardiography: a noninvasive method to predict high filling pressures in patients with coronary artery disease.” American Heart Journal 116(4): 1017-1021 (1988). Kidawa M et al. “Comparative value of tissue Doppler imaging and m-mode color Doppler mitral flow propagation velocity for the evaluation of left ventricular filling pressure.” Chest 128(4):2544-2550 (2005)). E/E′, Epeak, Epeak/Apeak, Adur, velocity of propagation (Vp), Epeak/Vp, DT, isovolumic relaxation time (IVRT), and Adur−Ardur have all been tested as noninvasive estimates of LVEDP. While each index has shown marginal success in specific homogeneous patient groups, all non-invasive indexes, with the exception of E/E′ fail to correctly predict invasive pressures in patients with normal systolic function. This is a significant limitation because up to 50% of patients with heart failure suffer from diastolic heart failure with normal systolic function.
Accordingly, there remains a need for methods and related systems that provide a load-independent index of diastolic function, as well as a need for methods and related systems that provide a non-invasive measure of left ventricular operating pressures.